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Transcript of 2004 Exercise for People With Peripheral Neuropathy
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Exercise for people with peripheral neuropathy (Review)
White CM, Pritchard J, Turner-Stokes L
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2011, Issue 6http://www.thecochranelibrary.com
Exercise for people with peripheral neuropathy (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
http://www.thecochranelibrary.com/http://www.thecochranelibrary.com/
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T A B L E O F C O N T E N T S
1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . . . . . . . . . . . . . . . . . . .
5BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
11 ADDITIONAL SUMMARY OF FINDINGS . . . . . . . . . . . . . . . . . . . . . . . . . .
15DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
16 AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
17 ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
17REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
20CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
27DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.1. Comparison 1 Strengthening exercise versus no exercise, Outcome 1 Change in time taken for 6m comfortable
walk (seconds). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
Analysis 1.2. Comparison 1 Strengthening exercise versus no exercise, Outcome 2 Change in isokinetic knee extension
torque (Nm). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
Analysis 1.3. Comparison 1 Strengthening exercise versus no exercise, Outcome 3 Change in endurance at 80% MVC
(seconds). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Analysis 1.4. Comparison 1 Strengthening exercise versus no exercise, Outcome 4 Change in isokinetic knee flexion torque
(Nm). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Analysis 1.5. Comparison 1 Strengthening exercise versus no exercise, Outcome 5 Change in maximal isometric voluntary
contraction force (Nm). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
Analysis 2.1. Comparison 2 Lower limb strengthening and balance exercise versus upper limb strengthening exercise,
Outcome 1 % Change in activities specific balance confidence scale scores. . . . . . . . . . . . . . 30
Analysis 3.1. Comparison 3 Home exercise versus no exercise, Outcome 1 Change in average muscle scores. . . . 31
Analysis 3.2. Comparison 3 Home exercise versus no exercise, Outcome 2 Change in left handgrip force (Kg). . . . 31
Analysis 3.3. Comparison 3 Home exercise versus no exercise, Outcome 3 Change in right handgrip force (Kg). . . 32
32 APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
42 WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
42HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
43CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
43DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
43INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
iExercise for people with peripheral neuropathy (Review)
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[Intervention Review]
Exercise for people with peripheral neuropathy
Claire Margaret White1, Jane Pritchard2, Lynne Turner-Stokes3
1 Applied Biomedical Research Division, King’s College London, London Bridge, UK. 2 Neuromuscular Unit 3 North, Charing Cross
Hospital, London, UK. 3 Regional Rehabilitation Unit, King’s College London and Northwick Park Hospital, Harrow, UK
Contact address: Claire Margaret White, Applied Biomedical Research Division, King’s College London, Room 3.6, Shepherd’s House,
Guy’s Campus, London Bridge, London, SE1 1UL, UK. [email protected] .
Editorial group: Cochrane Neuromuscular Disease Group.Publication status and date: Edited (no change to conclusions), published in Issue 6, 2011.
Review content assessed as up-to-date: 23 September 2009.
Citation: White CM, Pritchard J, Turner-Stokes L. Exercise for people with peripheral neuropathy. Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No.: CD003904. DOI: 10.1002/14651858.CD003904.pub2.
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
A B S T R A C T
Background
Peripheral neuropathies are a wide range of diseases affecting the peripheral nerves. Demyelination or axonal degeneration gives rise to
a variety of symptoms including reduced or altered sensation, pain, muscle weakness and fatigue. Secondary disability arises and this
may result in adjustments to psychological and social function. Exercise therapy, with a view to developing strength and stamina, forms
part of the treatment for people with peripheral neuropathy, particularly in the later stages of recovery from acute neuropathy and in
chronic neuropathies.
Objectives
The primary objective was to examine the effect of exercise therapy on functional ability in the treatment of people with peripheral
neuropathy. In addition, secondary outcomes of muscle strength, endurance, broader measures of health and well being, as well as
unfavourable outcomes were examined.
Search methods
In September 2009 we updated the searches of the Cochrane Neuromuscular Disease Group register, MEDLINE (from January 1966),
EMBASE (from January 1980), CINAHL (from January 1982) and LILACS (from January 1982). Bibliographies of all selected
randomised controlled trials were checked and authors contacted to identify additional published or unpublished data.
Selection criteria
Any randomised or quasi-randomised controlled trial in people with peripheral neuropathy comparing the effect of exercise therapy
with no exercise therapy or drugs or an alternative non-drug treatment on functional ability (or disability) for at least eight weeks after
randomisation was included.
Data collection and analysis
Two authors independently selected eligible studies, rated the methodological quality and extracted data.
1Exercise for people with peripheral neuropathy (Review)
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Main results
Only one trial fully met the inclusion criteria. An additional two trials assessed outcomes less than eight weeks after randomisation
and were also included. Methodological quality was poor for several criteria in each study. Data used in the three studies could not be
pooled due to heterogeneity of diagnostic groups and outcome measures. The results of the included trials failed to show any effect of
strengthening and endurance exercise programmes on functional ability in people with peripheral neuropathy. However, there is some
evidence that strengthening exercise programmes were moderately effective in increasing the strength of tested muscles.
Authors’ conclusions
There is inadequate evidence to evaluate the effect of exercise on functional ability in people with peripheral neuropathy. The results
suggest that progressive resisted exercise may improve muscle strength in affected muscles.
P L A I N L A N G U A G E S U M M A R Y
Exercise for treating people with diseases of their peripheral nerves (peripheral neuropathy)
Peripheral neuropathies are a wide range of diseases (both genetic and acquired) affecting the peripheral nerves. Symptoms can include
pain, altered sensation such as tingling or numbness, muscle weakness and fatigue. Exercise therapy, with a view to improving strength
and stamina, forms part of many rehabilitation programmes after a peripheral neuropathy. This review found inadequate evidence
from randomised controlled trials to evaluate the effect of exercise in disability in peripheral neuropathy. There was evidence that
strengthening exercises moderately improve muscle strength in people with a peripheral neuropathy.
2Exercise for people with peripheral neuropathy (Review)
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S U M M A R Y O F F I N D I N G S F O R T H E M A I N C O M P A R I S O N [ Explanation ]
Strengthening exercise versus no exercise for people with peripheral neuropathy
Patient or population: patients with people with peripheral neuropathySettings:
Intervention: Strengthening exercise versus no exercise
Outcomes Illustrative comparative risks* (95% CI) Relative effect
(95% CI)
No of Participants
(studies)
Quality
(GRADE
Assumed risk Corresponding risk
Control Strengthening exercise
versus no exercise
Change in time taken
for 6m comfortable walk (seconds)
Follow-up: 8 weeks
The mean change in time
taken for 6m comfort-able walk(seconds)in the
control groups was
0.3 seconds
The mean Change in time
taken for 6m comfortablewalk (seconds) in the in-
tervention groups was
0.7 higher
(0.23 to 1.17 higher)
26
(1 study)
⊕⊕⊕
modera
Change in isokinetic
knee extension torque
(Nm)
Follow-up: 8 weeks
The mean change in
isokinetic knee extension
torque (nm) in the control
groups was
-5.3 Newton metres
The mean Change in
isokinetic knee extension
torque (Nm) in the inter-
vention groups was
17.7 higher
(5.11 to 30.29 higher)
26
(1 study)
⊕⊕⊕
modera
Change in endurance at
80% MVC (seconds)
Follow-up: 8 weeks
The mean change in en-
durance at 80% mvc
(seconds) in the control
groups was
1.5 seconds
The mean Change in en-
durance at 80% MVC
(seconds) in the interven-
tion groups was
0.3 higher
(11.04 lower to 11.64
higher)
23
(1 study)
⊕⊕⊕
modera
3
E x er ci s ef or p e o pl e
wi t h p er i ph er al n e ur o p a t h y ( R e vi e w )
C o p yr i gh t ©2 0 1 1 T
h e C o ch r an e C ol l a b or a t i on .P u b l i s h e d b y J oh n Wi l e y & S on s ,L t d .
http://www.thecochranelibrary.com/view/0/SummaryFindings.htmlhttp://www.thecochranelibrary.com/view/0/SummaryFindings.html
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Change in isokinetic
knee flexion torque
(Nm)
Follow-up: 8 weeks
Themeanchangeinisoki-
netic knee flexion torque
(nm) in thecontrol groups
was-1.1 Newton metres
The mean Change in
isokinetic knee flexion
torque (Nm) in the inter-
vention groups was0.5 lower
(9.78 lower to 8.78
higher)
26
(1 study)
⊕⊕⊕
modera
Change in maximal iso-
metric voluntary con-
traction force (Nm)
Follow-up: 8 weeks
The mean change in max-
imal isometric voluntary
contraction force (nm) in
the control groups was
4 Newton metres
Themean Changein max-
imal isometric voluntary
contraction force (Nm) in
the intervention groups
was
12.6 higher
(1.51 lower to 26.71
higher)
26
(1 study)
⊕⊕⊕
modera
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and
assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval;
GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimat
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the es
Very low quality: We are very uncertain about the estimate.
1 High risk of bias for sequence generation, allocation concealment, blinding and incomplete outcome data.
4
E x er ci s ef or p e o pl e
wi t h p er i ph er al n e ur o p a t h y ( R e vi e w )
C o p yr i gh t ©2 0 1 1 T
h e C o ch r an e C ol l a b or a t i on .P u b l i s h e d b y J oh n Wi l e y & S on s ,L t d .
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B A C K G R O U N D
Peripheral nerves connect the sensory receptors and muscles to
the central nervous system. Peripheral nerves are subject to a very
wide range of diseases called peripheral neuropathies that collec-
tively affect about 2.4% of the population (Martyn 1998). The
peripheral neuropathies are a heterogeneous group of disorders in
which one or all of the elements of the peripheral nervous system
are damaged, primarily affecting either the myelin (the nerve in-
sulating sheath), the axon (the central nerve fibre), or a mixture
of the two. Damage to the myelin sheath, or demyelination, pro-
duces dysfunction which may be quite rapidly reversed in a matter
of weeks as the myelin regenerates. Damage to the nerve axon is
repaired by regeneration or sprouting from the intact elements,
which may take many months and recovery is often incomplete.
Patients with peripheral neuropathy typically develop symptomsof numbness, or altered sensation (e.g. pins and needles), starting
at the extremities and progressing more proximally with advancing
disease. Strength is affected when motor nerves are involved. Re-
duced or absent reflexes are a characteristic examination finding.
Peripheral neuropathies can be genetic or acquired. Some may
be insidious in onset whilst others are acute. The natural his-
tory in any individual case of neuropathy is largely dependent
upon the underlying cause. Acute neuropathies, such as Guillain-
Barré syndrome, reach their worst and then slowlyrecover. Others,
e.g. chronic inflammatory demyelinatingpolyradiculoneuropathy,
tend to relapse and remit, whilst others gradually deteriorate over
many years (e.g. Charcot-Marie-Tooth disease (CMT), alcohol-
related neuropathy).
Symptoms during and residual problems after peripheral neuropa-
thy include muscle weakness, pain, sensory deficits, increased fati-
gability (Merkies 1999), psychological dysfunction and difficulties
with poor social adjustment (Lennon 1993; Pfeiffer 2001; Padua
2008). The extent of an individual’s physical recovery is not neces-
sarily related to recovery of nerve function (Molenaar 1999). As in
other chronic neurological disorders, the extent to which individ-
uals with similar residual deficits experience limitations in activity
and how they perceive the impact of this on their daily lives varies
(Lennon 1993; Nicholas 2000).
Rehabilitation for people after peripheral neuropathy has focused
on symptomatic treatment and exercise therapy with little agree-
ment in the literature regarding whetherstrengthening (Lindeman
1995) or endurance (Pitetti 1993) programmes are more effective
(Herbison 1983).
However, several uncontrolled studies since the last update of this
review, show that exercise interventions are associated with sig-
nificant improvements in muscle strength, functional ability and
fatigue (Chetlin 2008; Garssen 2004; Graham 2007). Recent rec-
ommendations for exercise prescription for people with periph-
eral neuropathy include a combination of aerobic and functional
exercises as well as strengthening exercises to target specific weak
muscle groups (Chetlin 2004; Hughes 2005).
Strengthening programmes typically involve progressive resisted
exercise utilising repetitions of specific muscle contractions. Thesecan be isometric (performed against maximal resistance where no
associated jointmovementis possible),isotonic(performedagainst
a submaximal known resistance, this is typically greater than 70%
of the maximal load possible, where joint movement and limb
excursion is permitted) or isokinetic (performed against variable
resistance but where the speed of contraction is constant). En-
durance programmes typically involve gradually increasing the du-
ration and intensity of aerobic activity for example cycling, run-
ning, or walking. Specific muscle endurance programmes may also
involve the use of low load high repetition muscle contractions.
Patients are often unsure as to how much exercise they should un-
dertake in both acuteneuropathy, which is recovering, and chronicneuropathy, in which their exercise tolerance is reduced. They can
be fearful that excessive exercise might exacerbate their symptoms.
Indeed, insome patients where markedweaknessis a feature, joints
may be at a mechanical disadvantage and exercising may result in
soft tissue damage.
There is some consensus that fatigue may be a common feature
in people with peripheral neuropathy (Merkies 1999). The car-
diorespiratory response to exercise testing has been shown to be re-
duced in people with CMT (Carter 1995) and subclinical deficits
in aerobic capacity and/or muscular strength and endurance are
revealed by army physical fitness testing (Burrows 1990) in sol-
diers after recovery from GBS.
Since the previous update, two cohort studies of exercise for peo-
ple with inflammatory neuropathy show that participants were
stronger, fitter and experienced less fatigue after a 12 week exer-
cise programme that included aerobic activity. The reduction in
fatigue was also associated with an improvement in overall mood
and quality of life (Garssen 2004; Graham 2007). The extent to
which subjective feelings of fatigue are related to objective muscle
fatigue is unclear. Thus graded exercise programmes such as those
which have been shown to be effective in improving functional
performance, and participation by people with chronic fatigue
syndrome (Fulcher 1997; Powell 2001; Wearden 1998) in RCTs
may be appropriate.
It has been suggested that judicious timing of exercise therapy is
necessary because evidence from animal studies suggests that in-
creased neuromuscular activity during reinnervation may be detri-
mental. Whilst there is some evidence that intensive exercise car-
ried out early in the reinnervation process is detrimental to nerve
sprouting (Tam 2001), the bulk of studies show either no effect
(Gardiner 1986; Sebum 1996) or a beneficial effect (Einsiedel
1994; Ribchester 1988) of exercise during reinnervation on the
recovery of function.
Therefore it is important to examine critically the evidence sur-
rounding the safety, type, timing and effectiveness of exercise in
the treatment of people with peripheral neuropathy.
5Exercise for people with peripheral neuropathy (Review)
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O B J E C T I V E S
The objective was to systematically review the evidence from ran-
domised clinical trials concerning the effect of exercise therapy on
peripheral neuropathy.
M E T H O D S
Criteria for considering studies for this review
Types of studies
Any randomised controlled trial (RCT) or quasi-randomised con-
trolled trial comparing exercise therapy to treat peripheral neu-
ropathy with no exercise therapy or drugs or an alternative form
of non-drug treatment, was included. Quasi-randomised trials are
those in which randomisation was intended but may be biased.
Types of participants
Trials including participants (adults or children) with a diagnosis
of peripheral neuropathy, including sensory, motor and combined
sensory and motor neuropathies were selected. Trials including
cases of poliomyelitis were not included. Trials involving cases of
local entrapment neuropathies with pain as the primary present-
ing feature (e.g. cervical radiculopathy, carpal tunnel syndrome
etc) were not included. The diagnosis of peripheral neuropathy
offered by the authors, provided that it stipulated the presence of
clinical impairment characteristic of peripheral neuropathy, was
accepted. Diagnoses dependent on symptoms suggestive of neu-
ropathy alone or neurophysiological abnormalities in the absence
of clinical signs, were not accepted.
Types of interventions
Trials including any form of exercise therapy including either pro-
gressive resisted exercise (isometric, isotonic or isokinetic) and/or
endurance training compared with either no exercise or drugs or
an alternative form of non-drug treatment, were selected.
Types of outcome measures
Primary outcomes
Functional ability at a timeframe less than eight weeks after the
start of the intervention/control period.
The review aimed to select only trials where the primary outcome
measure was a measure of functional ability (sometimes called dis-
ability or activity limitation ( WHO 2001)), as measured by a val-
idated tool, at least eight weeks after the start of the intervention/
control period. Functional ability may include measures of mobil-
ity such as walking, stair climbing and running, functional use of the affected arm/s and/or independence in activities of daily living
such as washing, dressing, preparing food etc.
Secondary outcomes
Secondary outcome measures included were those validated out-
come measures used to assess:
(1) muscle strength at least eight weeks after the start of the inter-
vention (or on completion of the exercise programme);
(2) endurance at least eight weeks after the start of theintervention
(or on completion of the exercise programme);
(3) psychological status or quality of life at least eight weeks after
the start of the intervention (or on completion of the exerciseprogramme);
(4) return to work at least twelve months after the start of the
intervention.
In addition unfavourable secondary outcomes were assessed in-
cluding:
(5) relapse as evidenced by an increase in neurological deficit;
(6) development or increase in pain sufficient to require the use,
or increased use, of analgesics.
Search methods for identification of studies
The Cochrane Neuromuscular Disease Group Register was
searched using ’neuritis’ or ’neuropathy’ or ’CIDP’ or ’guillainbarre’ or ’chronic inflammatory demyelinating polyradiculoneu-
ropathy’ or ’polyradiculoneuritis’ or ’polyneuropathy’ or ’polyneu-
ritis’ , combined using AND with ’strength training’ or ’endurance’
or ’exercise’ or ’physical therapy’ or ’physiotherapy’ or ’rehabilita-
tion’ as search terms in September 2009. MEDLINE (from 1966
to September 2009), EMBASE (from January 1980 to Septem-
ber 2009), CINAHL (from January 1982 to September 2009),
AMED (from January 1985 to September 2009) and LILACS
(January 1982 to September 2009) were searched using the search
strategy stated in the Cochrane Neuromuscular Disease Group
module in combination with terms used identify potential RCTs
(see below for strategy). Bibliographies of all selected RCTs were
checked and authors contacted to identify additional published orunpublished data.
Search methods for electronic databases
The search strategies used are listed in the Appendices: Appendix
1, Appendix 2, Appendix 3, Appendix 4, Appendix 5.
Data collection and analysis
Selection of studies
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Titles and abstracts identified by the search were checked by two
authors (CMW, JP). The full texts of all potentially relevant stud-ies were obtained and independently assessed by both authors.
The authors decided which trials fulfilled the inclusion criteria
and graded their methodological quality. Any disagreement about
inclusion criteria was resolved by discussion between the authors
without need for the third author.
Data extraction and management
The assessment of methodological quality of the trials was redone
for the 2009 update according to the methods now favoured by
the Cochrane Collaboration and published in Chapter 8 of the
Cochrane Handbook for SystematicReviews of Interventions (Higgins2008). Items considered were allocation concealment, participant
blinding, observer blinding, explicit diagnostic criteria, documen-
tation of therapy input, explicit outcome criteria, how studies deal
with baseline differences of experimental groups and completeness
of follow-up. The items were graded: low risk of bias, high risk
of bias or ’unclear’: unknown risk of bias or the entry was not
relevant in the study.
Assessment of risk of bias in included studies
Data extraction was performed independently by two authors us-
ing a standardised data extraction form.
Measures of treatment effect
Results were expressed as risk ratios (RR) with 95% confidence
intervals (CI) andrisk differences (RD) with 95% CIsfor dichoto-
mous outcomes and mean differences (MD) with 95% CIs for
continuous outcomes.
Data synthesis
Data from clinically homogenous studies were pooled where pos-
sible and sensitivity analysis undertaken for methodological qual-
ity.
Subgroup analysis and investigation of heterogeneity
Subgroups of interest were identified in advance and were chosen
for their prognostic importance. The subgroups were defined as
follows:
(a) type and mode of onset of neuropathy (ie type of neuropa-
thy either: hereditary, metabolic or inflammatory, mode of onset:
acute, relapsing or progressive);
(b) patients with less severe disease/disability (walks unaided) com-
pared with patients with severe disease (unable to walk or only
able to walk with assistance).
R E S U L T S
Description of studies
See: Characteristicsof included studies; Characteristicsof excluded
studies; Characteristics of studies awaiting classification.
The search strategy for the databases resulted in a list of 481 cita-
tions. The other searches did not add any further references. Au-
thors CMW and JP selected a total of 29 citations of full-length
articles and abstracts describing 28 exercise therapy trials. Out of
these, three trials reported in four full-length articles were identi-
fied as RCTs by the authors (Lindeman 1994a; Lindeman 1995;
Richardson 2001; Ruhland 1997). The two articles (Lindeman,1994a; Lindeman 1995) describe only one trial. For the purposes
of the review, only Lindeman 1995 will be referred to. Only one
trial fulfilled all selection criteria (Lindeman 1995) and will be
referred to as the primary included trial in the results section,
whilst a further two were included as they fulfilled all criteria ex-
cept the outcome criteria of primary and secondary outcomes at
least eight weeks after commencement of the intervention/control
period (Richardson 2001; Ruhland 1997). The two trials assessed
outcome on completion of shorter intervention and control pe-
riods, at three weeks (Richardson 2001) and six weeks (Ruhland
1997) after commencement and shall be referred to hereafter as
the secondary included trials in the results section.
The three identified trials included 82 patients with peripheralneuropathy of either hereditary (37 patients), inflammatory (25
patients) or metabolic (20 patients) aetiology. There were no trials
involving patients with acute peripheral neuropathy e.g. Guillain-
Barré syndrome (GBS) or recent drug or toxin exposure. The tri-
als were of similar sizes. The trial by Lindeman et al. (Lindeman
1995) recruited 34 patients with CMT disease: 21 subjects had
type I, six had type II and in two subjects the type was unknown.
Richardson (Richardson 2001) recruited 20 subjects with periph-
eral neuropathy associated with diabetes mellitus. Ruhland and
Shields (Ruhland 1997) recruited 28 subjects with chronic pe-
ripheral neuropathy including 12 with chronic inflammatory de-
myelinating polyradiculoneuropathy (CIDP), six with CIDP with
monoclonal gammopathy, three with CIDP with central demyeli-nation or possible toxic neuropathy, four with idiopathic axonal
degeneration and three with hereditary peripheral neuropathy.
Two trials compared progressive resisted exercise with a non-inter-
vention control (Lindeman 1995; Ruhland 1997). One of these
included aerobic conditioning exercise alongside progressive resis-
tance exercises (Ruhland 1997). The third trial compared progres-
sive resisted exercise and balance exercises with a non-therapeutic
exercise control (Richardson 2001). The non-therapeutic exercises
consisted of progressive resisted exercises of muscle groups in the
upper limb that were considered unlikely to influence the selected
focal lower limb outcome measures of unipedal stance, tandem
stance, functional reach and the activities specific balance scale.
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Electronic searches were updated prior to submission of the review
and a further potentially relevant study, published only in abstractform, was identified from the Cochrane Neuromuscular Disease
Group Register (Zifko 2003). The study is included in the studies
awaiting assessment since theauthors are currently seeking to pub-
lish the study in full. The information from the full publication
will be included in the review as an update, once available.
Risk of bias in included studies
Since blinding of patients and researchers is difficult in exercise
trials, the trials are susceptible to bias including detection, perfor-
mance and attrition bias. Even in the trial where participants were
randomised into active exercising and control exercising groups,the very different nature of the exercises (upper versus lower limb)
and the use of outcome measures reflecting lower limb function,
could prevent true patient blinding to the intervention.
The methods of randomisation were unclear in one trial (
Lindeman 1995) and inadequate in the other two (Richardson
2001; Ruhland 1997) due to matching of subjects in intervention
and control groups. Allocation concealment was not described in
any trial and in both trials where randomisation with matching
was carried out, allocation concealment was not possible.
Only one of the three trials included explicit diagnostic criteria.
Richardson (Richardson 2001) included patients with a known
history of diabetes mellitus and lower extremity symptoms con-
sistent with peripheral neuropathy. They also required conclusiveelectrodiagnostic evidence of diffuse, primarily axonal, peripheral
polyneuropathy. In the second trial Lindeman (Lindeman 1995)
includedpatientsdiagnosed with CMT disease on thebasisof their
clinical picture, electromyography and nerve conduction studies
but not genetic testing. However, no explicit details of diagnostic
criteria were given. In the third trial the criteria were not explicitly
stated and subjects were selected on the basis of their clinical di-
agnosis as recorded in a clinical database. Subjects were included
if they had a clinical diagnosis of CIDP, chronic idiopathic axonal
degeneration, CMT disease or toxic neuropathy as long as the
toxin was no longer detectable through blood sampling (Ruhland
1997). Duration, severity or degree of recovery from neuropathy
was not indicated in any of the included trials and baseline com-parisons of groups were made on the basis of other characteristics.
All trials considered differences in baseline characteristics, al-
though this was based on different clinical characteristics in each
case. There was no consistent examination of severity or dura-
tion of neuropathy. The first trial matched patients on muscle
strength and stair-climbing performance and no obvious base-
line differences in age or gender of patients was noted (Lindeman
1995). The second trial, where group randomisation was per-
formed, showed significant baseline differences in severity of neu-
ropathy as indicated by the Michigan Diabetes Neuropathy Score
(MDNS) (Richardson 2001). Eight out of the 28 patients in the
final trial were non-randomly placed into control and experimen-
tal groups to maintain similar baseline characteristics for age and
gender (Ruhland 1997). In this trial there were significant differ-ences in the Short Form-36 questionnaire (SF-36) for role limita-
tion (emotional) and social function scale scores and despite non-
randomised placement of patients, the mean age of patients in the
intervention group (63.6 ± 10.5 years) was significantly higher
than the control group (52.9 ± 16.2 years). However in this case
baseline differences were accounted for by using these factors as
co-variates in the subsequent data analysis.
In two trials the inclusion criteria included a minimum ambula-
tory capability of: “must be able to walk household distances with-
out assistance or assistive device indoors” (Richardson 2001) and,
“the ability to ambulate 4.6 m with or without assistance or assis-
tive device”’(Ruhland 1997). In the third trial there was no such
requirement but the baseline data included a stair climbing test,and a “qualification period” for recruited subjects was employed
to exclude subjects with motivational problems (Lindeman 1995).
Thus, it appears that only ambulant patients were included in the
reviewed studies.
Documentation of therapy input was adequate in two trials
(Lindeman 1995; Ruhland 1997). Clear descriptions of type, in-
tensity and duration of exercise were given in both cases. In the
third trial (Richardson 2001) the intensity and frequency of ex-
ercise was less in the control group than the intervention group
exposing the trial to moderate risk of bias.
Clear descriptions of outcome criteria were included in all tri-
als. The authors initially planned that only trials where the out-
come measures utilised validated measures of disability at leasteight weeks after randomisation, would be selected. However this
retrieved only one suitable study (Lindeman 1995). Under these
circumstances it was decided to include those studies where suit-
able outcome measures had been utilised on completion of an ex-
ercise programme, even where the programme was less than eight
weeks in duration. This alteration to the original protocol subse-
quently retrieved two further suitable studies (Richardson 2001;
Ruhland 1997). No included trial had disability as the primary
outcome measure. In one case the primary outcome measure, the
SF-36, was described as a measure of health related quality of life
(Ruhland 1997). Whilst it might be argued that this instrument
includes some items relating to disability, its primary focus is on
handicap (participation) and quality of life and it does not pro-vide data which could be combined in any robust way with the
commonly used standard measures of disability.
In one trial follow-up was complete for the intended follow-up
period(Ruhland 1997) and an intention-to-treat analysis was pos-
sible. In the two other trials, follow-up was incomplete due to
drop-outs. In the case of (Lindeman 1995) one control patient
was unable to undertake the final 24 week follow-up strength as-
sessments, due to knee problems. There was no attempt to re-
place data for intention to treat analyses and the matched pair to
which the control patient belonged was removed from the analysis.
In the other trial (Richardson 2001) one intervention and three
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control patients dropped out during the course of the trial. The
intervention patient dropped out due to exercises aggravating anunderlying arthritic condition, two control patients dropped out
giving no reason and the final control patient developed an un-
related illness, preventing completion of the trial. Follow-up was
not extended beyond the length of the intervention period in any
of the included trials. The intervention periods varied as follows:
three weeks (Richardson 2001), six weeks (Ruhland 1997) and 24
weeks (Lindeman 1995).
None of the trials fulfilled all of the criteria for methodological
quality and all three trials failed to reach adequate methodological
quality in a number of items. The scores for each trial for the risk
of bias are summarised in Figure 1. In addition the criterion for
patient blinding was waived in the case of exercise versus non-
exercise trials.
Figure 1. Methodological quality summary: review authors’ judgements about each methodological quality
item for each included study.
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Effects of interventions
See: Summary of findings for the main comparison
Strengtheningexercise versusno exercise for people withperipheral
neuropathy ; Summary of findings 2 Lower limb strengthening
and balance exercise versus upper limb strengthening exercise
for people with peripheral neuropathy ; Summary of findings
3 Home exercise versus no exercise for people with peripheral
neuropathy
Authors decided by consensus not to pool data because of the
differences in presentation of the results as well as the variety of
outcome measures used.
Intheprimaryincludedtrial(Lindeman 1995)meanchangescores with standard deviations were presented. In the two secondary in-
cluded trials, mean baseline and follow-up scores with standard
deviations were presented, in addition to mean change scores with
standard deviations (Richardson 2001; Ruhland 1997). The re-
view will present data as mean change scores where possible.
Primary outcome measure
The primary included trial showed a significant reduction in the
time taken for a six metre walk (Lindeman 1995) at 24 weeks after
starting the exercise with a MD of 0.7 (95% CI 0.23 to 1.17)
( Analysis 1.1). No other significant improvements in time scored
functional activities were observed. There were no data avail-
able for the stated apparent improvement in aspects of upper-leg
strength related functional activities of the modified Western On-
tario and McMaster University Osteoarthritis Index (WOMAC)
used in this study. One of the two secondary included trials, used
the SF-36 to assess what the authors stated to be health related
quality of life (Ruhland 1997). However the SF-36 scale, in addi-
tion to the majority of items pertaining to an individuals level of
participation, also contains items pertaining to physical function-
ing. These items assess functional ability and could therefore more
readily be interpreted as relating to activity limitation. However,
no within or between group differences were found for the physi-
cal function scale. Unfortunately, no standard deviations were pre-
sented in the text of this study so no overall effect size can be cal-culated. In the final trial there were no significant changes in the
chosen disability outcome measure, the Activities Specific Balance
Confidence (ABC) scale score (Richardson 2001) at three weeks
after randomisation, MD 8.00 (95% CI -8.47 to 24.47) ( Analysis
2.1).
The follow-up duration was different in each trial. In the primary
included trial,follow-up was at eight weeklyintervalsfor 24 weeks.
However, in the secondary included trials the follow-upperiod was
less than the stated eight weeks recommended by the review proto-
col. Since, in these trials the duration of the exercise intervention
was also less than eight weeks, in one only three weeks (Richardson
2001) and in the other only six weeks (Ruhland 1997), shorter
follow-up periods were permitted.
Secondary outcome measures:
Muscle strength at follow-up
Significant improvements in isokinetic knee extension torque in
the exercise group at 24 weeks after starting the programme were
reported by Lindeman 1995 with an effect size of 17.7 (95% CI5.11 to 30.29) ( Analysis 1.2). However, there was no improve-
ment in knee flexion torque, MD -0.50 (95% CI -9.78 to 8.78)
( Analysis 1.4) or maximal isometric voluntary contraction force,
MD 12.6 (95% CI -1.51 to 26.71) ( Analysis 1.5).In the secondary
included trials, where outcomes were assessed at less than eight
weeks after commencement of the intervention/control period, a
fixed effects analysis showed that there was a greater change in
average muscle scores (AMS) for the exercise group than the con-
trol and significant within group improvements in AMS reported
by Ruhland (Ruhland 1997), MD 0.60 (95% CI 0.29 to 0.91)
( Analysis 3.1). Standard deviations were estimated from the pub-
lished paired t test P values with the help of a statistician. No
significant changes in right handgrip MD 1.70 (95% CI -0.60 to
4.00) ( Analysis 3.3) or left handgrip, MD 0.30 (95% CI -2.03 to
2.63) ( Analysis 3.2) were shown. Muscle strength was not assessed
in one trial (Richardson 2001).
Endurance at follow-up
The primary included trial utilised the maximum duration of con-
traction at 80%maximumvoluntary contraction (MVC) as a mea-
sure of muscle endurance (Lindeman 1995) but there was no im-
provement in the duration of a sustained 80% maximal voluntary
contraction force following 24 weeks of exercise. The MD was
0.3 (95% CI -11.04 to 11.64) ( Analysis 1.3). The two secondary
included trials did not assess endurance.
Psychological status or quality of life at follow-up
Theprimary included trial (Lindeman 1995) didnot assess quality
of life. Only one of the secondary included trials assessed quality
of life using the SF-36 (Ruhland 1997). It should be noted that
this measure also includes items that assess functional ability and
mobility. The study reported no significant improvement in psy-
chological status or quality of life and since no standard deviations
were presented in the text, no overall effect size may be calculated.
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Return to work at 12 months after randomisation
This was not measured in any of the included trials.
Unfavourable outcomes
Relapse as defined by an increase in neurological deficit
This was not measured in any of the included trials.
Pain
This was not consistently reported in the included trials. In the
primary included trial, one control patient dropped out due to
knee pain prior to final follow-up (Lindeman 1995). In one of the secondary included trials, one exercising patient dropped out
during the intervention period due to ankle pain (Richardson
2001).
Subgroup analysis
Theinformationreportedin theincludedtrials wasinsufficient forclearly identifying data for the subgroups of interest. In addition,
due to the variety of outcome measures used, pooling of data was
not appropriate. The primary included trial included only CMT
as a cause of peripheral neuropathy (Lindeman 1995). In the two
secondary included trials the participants had a diagnosis of dia-
betes-related diffuse primarily axonal peripheral polyneuropathy
in one trial (Richardson 2001) and predominantly presumed in-
flammatory neuropathies (25 patients) or hereditary neuropathy
(three patients) in the other (Ruhland 1997).
We had planned to pool data from clinically homogeneous studies
for meta-analysis, however this was not possible due to differences
in outcomes and interventions between studies. As a consequence, we did not conduct a sensitivity analysis for methodological qual-
ity. Therefore no analysis of the subgroups of interest (type of neu-
ropathy and disease severity) was possible.
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A D D I T I O N A L S U M M A R Y O F F I N D I N G S [ Explanation ]
Lower limb strengthening and balance exercise versus upper limb strengthening exercise for people with peripheral neuropathy
Patient or population: patients with people with peripheral neuropathySettings:
Intervention: Lower limb strengthening and balance exercise versus upper limb strengthening exercise
Outcomes Illustrative comparative risks* (95% CI) Relative effect
(95% CI)
No of Participants
(studies)
Quality
(GRADE
Assumed risk Corresponding risk
Control Lower limb strengthen-
ing and balance exer-
cise versus upper limb
strengthening exercise
% Change in activities
specific balance confi-
dence scale scores
ABC scale. Scale from: 0
to 100.
Follow-up: 3 weeks
The mean % change in
activities specific balance
confidence scale scores
in the control groups was
80 score
The mean % Change in
activities specific balance
confidence scale scores
in the intervention groups
was
8 higher
(8.47 lower to 24.47
higher)
16
(1 study)
⊕⊕⊕
modera
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and
assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval;
GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimat
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the es
Very low quality: We are very uncertain about the estimate.
1 High risk of bias for sequence generation, allocation concealment and incomplete outcome data and uncertain risk of bias for blinding1 2
E x er ci s ef or p e o pl e
wi t h p er i ph er al n e ur o p a t h y ( R e vi e w )
C o p yr i gh t ©2 0 1 1 T
h e C o ch r an e C ol l a b or a t i on .P u b l i s h e d b y J oh n Wi l e y & S on s ,L t d .
http://www.thecochranelibrary.com/view/0/SummaryFindings.htmlhttp://www.thecochranelibrary.com/view/0/SummaryFindings.html
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Home exercise versus no exercise for people with peripheral neuropathy
Patient or population: patients with people with peripheral neuropathy
Settings:Intervention: Home exercise versus no exercise
Outcomes Illustrative comparative risks* (95% CI) Relative effect
(95% CI)
No of Participants
(studies)
Quality
(GRADE
Assumed risk Corresponding risk
Control Home exercise versus
no exercise
Change in average mus-
cle scores
AMS.Scale from: 0 to10.Follow-up: 6 weeks
The mean change in aver-
age muscle scores in the
control groups was8.6 score
Themean Changein aver-
age muscle scores in the
intervention groups was0.6 higher
(0.29 to 0.91 higher)
28
(1 study)
⊕⊕⊕
modera
Change in left handgrip
force (Kg)
Follow-up: 6 weeks
The mean change in left
handgrip force (kg) in the
control groups was
28.9 kilograms
The mean Change in left
handgrip force (Kg) in the
intervention groups was
0.3 higher
(2.03 lower to 2.63
higher)
28
(1 study)
⊕⊕⊕
modera
Change in right handgrip
force (Kg)
Follow-up: 6 weeks
The mean change in right
handgrip force (kg) in the
control groups was29.1 kilograms
The mean Change in right
handgrip force (Kg) in the
intervention groups was1.7 higher
(0.6 lower to 4 higher)
28
(1 study)
⊕⊕⊕
modera
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and
assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval;
1 3
E x er ci s ef or p e o pl e
wi t h p er i ph er al n e ur o p a t h y ( R e vi e w )
C o p yr i gh t ©2 0 1 1 T
h e C o ch r an e C ol l a b or a t i on .P u b l i s h e d b y J oh n Wi l e y & S on s ,L t d .
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GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimat
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the esVery low quality: We are very uncertain about the estimate.
1 High risk of bias for sequence generation, allocation concealment and blinding.
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx
1 4
E x er ci s ef or p e o pl e
wi t h p er i ph er al n e ur o p a t h y ( R e vi e w )
C o p yr i gh t ©2 0 1 1 T
h e C o ch r an e C ol l a b or a t i on .P u b l i s h e d b y J oh n Wi l e y & S on s ,L t d .
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D I S C U S S I O N
The main finding of the review is that there is insufficient evidenceavailable from randomised controlled trials to confidently evaluate
the effect of exercise on functional ability in patients with periph-
eral neuropathy. Only one trial examining the effect of exercise
in 34 patients with CMT met the full inclusion criteria and was
initially included in the review (Lindeman 1995). Subsequently, a
furthertwo trialsthat metall criteria except forthe need forstudies
to examine follow-up at least eight weeks after commencement of
the intervention or control period, were also included (Richardson
2001; Ruhland 1997). All three trials were small with only 82 pa-
tients examined in total. The authors acknowledge that blinding
of patients and to a lesser extent observers is difficult in exercise
therapy trials. If blinding is carried out, it generally remains at
least at risk of exposure and hence bias, and therefore these cri-
teria for methodological quality are difficult to satisfy. Neverthe-
less, the included trials failed to meet several of our other criteria
for methodological quality and this inevitably limits the certainty
with which any conclusions may be viewed.
Interpreting the findings from included trials
The cause of neuropathy was different in each trial (metabolic,
CMT disease, CIDP) and mixed causes were evident in one trial
(Ruhland 1997). The severity of disease and the duration since
onset was not adequately documented in the three trials. However,inclusion and exclusion criteria based on functional mobility may
have reduced variability of these factors in the reviewed trials.
Nevertheless, the response to exercise in patients with different
types, severity and/or duration of peripheral neuropathy may be
different and therefore reduce the validity and generalisability of
findings.
Whilst all trials included exercises to improve muscle strength, the
intensity of exercise was variable and the muscle groups strength-
ened were different across the three trials. Only Lindeman 1995
utilised a standardised method of determining load for exercise
intensity. Ruhland 1997 used progressive strengthening exercises
determined by the subjects ease of completion and the final study (Richardson 2001) used a fixed load with increased repetitions
during the intervention period. Both studies using progressive re-
sistance (Lindeman 1995; Ruhland 1997) demonstrated some sig-
nificant improvements in muscle strength over the period of the
intervention.
The effect of exercise on cardiovascular fitness was not evaluated
in any of the included trials, despite the inclusion of 20 minutes of
aerobic cycling in the training programme for one study (Ruhland
1997). This is an unfortunate omission since the evidence from
RCTs for the benefits of regular exercise on improving cardiovas-
cular fitness (Lemura 2000; McArdle 1996), mood and mental
well-being in the general population (McAuley 2000; Moses 1989)
and in patients with neuromuscular disorders (Cedraschi 2004) is
growing.
Reporting of outcome measures
A lack of consensus in reporting of outcome measures was evident
inthereview.Whilstalltrialsusedbetweenoneandfivetimescored
functional activities to assess functional ability no single activity
was the same across trials. Two trials used additional measures,
namely, subscales of the SF-36 (Ruhland 1997) or a modification
of the functional component of the WOMAC (Lindeman 1995)
to assess functional ability. However, it couldbe argued that neither
of these measures unequivocally evaluates functional ability since
they include questions to evaluate the impact of deficits in func-tional ability on general functioning or societal participation. No
significant changes in the composite measures were demonstrated.
Indeed, only an improvement in the six metre comfortable walk-
ing speed at 24 weeks after starting the exercise programme was
demonstrated by Lindeman 1995.This suggests that exercise may
have a limited effect on functional ability, at least in the reviewed
trials. However, the authors suggested that this small change in
preferred six metre gait speed may be influenced by motivation
since the subjects were not blinded for intervention allocation. It
is also important to note that the intervention period in two of
the trials was less than the eight weeks initially identified by the
review protocol. It could be that in these trials (Richardson 2001;
Ruhland 1997) the exercise was not continued for long enough.Indeed, Lindemanet al.(Lindeman 1995) did notreport improve-
ments in any of the measures of functional ability at either of the
earlier time points for assessing outcome (eight and 16 weeks after
starting exercising).
Secondary outcomes
Of the stated secondary outcomes, muscle strength, endurance
and quality of life were evaluated in some of the included tri-
als. The only beneficial effects of exercise presented were small
but significant changes in muscle force which were demonstrated
in two trials (Lindeman 1995; Ruhland 1997) with the greatestimprovement in strength observed where the methods for deter-
mining load for progressive resisted exercise was clearly described
and standardised (Lindeman 1995). The authors claim that this
change in muscle strength represents only a moderate improve-
ment in response to strengthening exercise compared with healthy
people (Hakkinen 1985). However the response to strengthening
exercise varies due to the type, intensity and duration of exercise
and the percentage change in strength of leg extensors in this study
is comparable with more recent studies of similar interventions
in patient populations and healthy exercising controls (Hakkinen
2001; Valkeinen 2004). Interestingly, it is well recognised that
whilst there are early increases in muscle strength due to train-
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ing ( Young 1985) these are largely due to improved neural effec-
tiveness and changes to muscle structure take longer to establish(Moritani 1979).Thus improvements in muscle strength may not
be sufficient in the shorter trials to have an impact on functional
ability. The modest evidence from this review supports the view
that progressive resisted exercise may be effective in improving
muscle strength in people with peripheral neuropathy.
Adverse effects of exercise
Only one participant who was undertaking exercise dropped out
of the trial (Richardson 2001) due to pain in the lower limb.
This was attributed to the programme aggravating an underlying
arthritic condition. No other adverse events were documented.This is an important finding for two reasons. Firstly, it should be
noted that in peripheral neuropathy, where motor and/or sensory
signs and symptoms are present, altered joint mechanics and mus-
cle imbalance may predispose patients to soft tissue injury during
exercise. The included trials did not discuss this or the use of or-
thotic support to protect affected joints during exercise. Secondly,
controversy exists regarding the use of strengthening exercises in
conditions where partial denervation and reinnervation may be a
feature. The possibility of overwork leading to an increase in neu-
rological signs and symptoms has been investigated in both animal
and human studies. Recent evidence from animal studies suggests
that during the early reinnervation phase after partial denervation
high levels of neuromuscular activity as a result of electrical stim-ulation or exercise prevents axonal sprouting and increases motor
unit loss (Tam 2001). However in people with post-poliomyelitis
where enlarged motor units are compensating for progressive ax-
onal loss due to partial denervation, moderate intensity exercise
was effective in increasing muscle strength with no deleterious ef-
fects on motor unit number (Chan 2003). Therefore the limited
evidence available from this review and others evaluating the effect
of exercise in people with similar problems such as in fibromyal-
gia syndrome (Busch 2004) and physical disability in older peo-
ple (Latham 2004) suggests that exercise programmes aimed at
strengthening muscles are feasible in people with peripheral neu-
ropathy.
Limitations of the review
The search strategy of the review identified 481 citations, of which
only one trial fulfilled all the selection criteria and a further two
trials met all but one of the criteria. This highlights the paucity of
trials and evidence in this important area of investigation. Several
factors regarding the patient group and type of intervention may
be responsible for this. Firstly, despite the relatively high preva-
lence of peripheral neuropathy in the population (Martyn 1998)
the varied diagnostic types and severity of disease makes recruit-
ment to trials of large numbers of sufficiently similar participants
difficult. Secondly, the willingness of participants to be randomly
allocated into either an exercise or non-intervention control groupis particularly important for exercise trials where the motivation
and commitment of the individual participants to undertake the
exercise component may deter them from agreeing to participate.
Finally, the current clinical provision for patients with peripheral
neuropathy is likely to be predominantly by individualised reha-
bilitation that may include prescription of exercise in response to
patients symptoms and individual needs. In addition many peo-
ple with stable or chronic peripheral neuropathy may not be in
receipt of treatment for their symptoms. This means that accu-
rate description of exercise therapy in clinical trials is not always
documented. This final point is important since the continued
lack of high quality evidence regarding the efficacy of exercise in
the treatment of people with peripheral neuropathy may influencethe availability, accessibility and quality of service provision for
this client group. Medical charities (NAlliance 2002) and others
(DoH 2004) have identified the needs of people with neurological
and/or chronic conditions and service provision is a major con-
cern. No true assessment of the cost and benefits of exercise in
the treatment of people with peripheral neuropathy can be made
until relevant research evidence is available, including the effect
of exercise treatment on the overall economic burden of care to
health service providers.
Overall the results of theincludedtrials didnot show that strength-
ening and endurance exercise programmes improve functional
ability or reduce disability in patients with peripheral neuropa-
thy. However, there was limited evidence that strengthening exer-cise programmes were effective in increasing the strength of tested
muscles (Lindeman 1995; Ruhland 1997). There was no impact
on the level of disability in these patients but this may be related
to the duration of the exercise intervention and methodological
quality of included trials.
Limitations in the methods of the review
Whilst two authors were independently involved in checking titles
and abstracts identified by the search, in assessing potentially rel-
evant studies for inclusion and in evaluating the methodological
quality of included studies, disagreements regarding inclusion cri-teria andqualitywere resolved by discussion andit wasnot deemed
necessary to refer these to a third author. In addition whilst a stan-
dardised data extraction sheet was devised by two authors (CMW,
JP) no wider consultation of experts in the field, regarding the
content of the data extraction form was carried out. It is possible
that these omissions may have introduced some personal bias in
interpretation of the studies for inclusion in the review.
A U T H O R S ’ C O N C L U S I O N S
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Implications for practice
There is little evidence from the presented RCTs to evaluate the
effect of exercise on functional ability in peripheral neuropathy.
The included trials failed to meet some of the selected criteria
for risk of bias and the outcome measures used were too varied
for accurate comparisons. However, there is some evidence that
strengthening exercises moderately improve muscle strength in
tested muscles.
No further RCTs were identified in the current update thus, clini-
cal guidelines must remain based largely on evidence from uncon-
trolled trials.
Implications for research
The lack of high quality evidence with which to evaluate the effect
of exercise on functional ability in people with peripheral neu-
ropathy strongly supports the need to develop future high qual-ity sufficiently powered trials. Future research designs should con-
sider compatible diagnostic groups and include adequate alloca-
tion concealment, blinding of outcome assessor, clear description
of exercise intervention and standardization of outcome measures.
A C K N O W L E D G E M E N T S
Professor RAC Hughes for advice and comments, Ms K Jewitt
for practical assistance and training in the use of Review Man-
ager. Editorialsupport from the Cochrane Neuromuscular Disease
Group was funded by the TREAT NMD European Union Grant036825.
R E F E R E N C E S
References to studies included in this review
Lindeman 1995 {published data only}
Lindeman E, Drukker J. Specificity of strength training in
neuromuscular disorders. Journal of Rehabilitation Sciences 1994;7(Suppl):13–15.∗ Lindeman E, Leffers P, Spaans F, Drukker J, Reulen J,
Kerckhoffs M, et al.Strength training in patients with
myotonic dystrophy and hereditary motor and sensory
neuropathy: a randomized clinical trial. Archives of Physical Medicine and Rehabilitation 1995;76(7):612–20.
Richardson 2001 {published data only}
Richardson J, Sandman D. A focussed exercise regime
improves clinical measures of balance in patients with
peripheral neuropathy. Archives of Physical Medicine and
Rehabilitation 2001;82:205–9.
Ruhland 1997 {published data only}
Ruhland J, Shields R. The effects of a home exercise
programme on impairment and health related quality of life
in persons with chronic peripheral neuropathies. Physical
Therapy 1997;77(10):1026–39.
References to studies excluded from this review
Becker 1986 {published data only}
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LoVecchio 1997 {published data only}
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